Methods to deliver high intensity focused ultrasound to target regions proximate blood vessels

ABSTRACT

Methods for applying heat to a region proximate a blood vessel are disclosed. In one embodiment, a method can include generating an imaging ultrasound beam adapted to image a blood vessel target and receiving a reflection of the imaging ultrasound beam. The method can also include producing an output signal in response to the reflection of the imaging ultrasonic beam and processing the output signal to identify a location of a treatment zone proximate an outer wall of the blood vessel. Therapeutic energy can be applied to the treatment zone. In some embodiments, the therapeutic ultrasound energy beam can be moved to over-scan the treatment zone. Other methods are also disclosed.

RELATED APPLICATIONS

This application is a continuation of co-pending U.S. application Ser.No. 12/896,740, filed Oct. 1, 2010, which is a continuation of U.S.application Ser. No. 11/619,996, filed Jan. 4, 2007, which is acontinuation of co-pending U.S. application Ser. No. 10/616,831, filedJul. 10, 2003, which is a continuation of U.S. application Ser. No.09/696,076, filed Oct. 25, 2000, now U.S. Pat. No. 6,656,136, whichclaims the benefit of U.S. provisional patent application Ser. No.60/163,466, filed Oct. 25, 1999, and U.S. provisional patent applicationSer. No. 60/171,703, filed Dec. 23, 1999.

FIELD OF THE INVENTION

The present invention generally relates to methods and apparatus forsealing vascular punctures and wounds, and more particularly, to adevice that may be used to deliver ultrasound energy to a vascularpuncture site to arrest bleeding.

BACKGROUND OF THE INVENTION

Various surgical procedures are performed by medical specialists such ascardiologists and radiologists, utilizing percutaneous entry into ablood vessel. To facilitate cardiovascular procedures, a small gaugeneedle is introduced through the skin and into a target blood vessel,often the femoral artery. The needle forms a puncture through the bloodvessel wall at the distal end of a tract that extends through theoverlying tissue. A guide wire is then introduced through the bore ofthe needle, and the needle is withdrawn over the guide wire. Anintroducer sheath is next advanced over the guide wire; the sheath andguide wire are left in place to provide access during subsequentprocedure(s). The sheath facilitates passage of a variety of diagnosticand therapeutic instruments and devices into the vessel and itstributaries. Illustrative diagnostic procedures include angiography,intravascular ultrasonic imaging, and the like; exemplary interventionalprocedures include angioplasty, atherectomy, stent and graft placement,embolization, and the like. After this procedure is completed, thecatheters, guide wire, and introducer sheath are removed, and it isnecessary to close the vascular puncture to provide hemostasis and allowhealing.

The most common technique for achieving hemostasis is to apply hardpressure on the patient's skin in the region of the tissue tract andvascular puncture to form a blood clot. Initially, pressure is appliedmanually and subsequently is maintained through the use of mechanicalclamps and other pressure-applying devices. While effective in mostcases, the application of external pressure to the patient's skinpresents a number of disadvantages. When applied manually, the procedureis time-consuming and requires the presence of a medical professionalfor thirty minutes or more. For both manual and mechanical pressureapplication, the procedure is uncomfortable for the patient andfrequently requires the administration of analgesics to be tolerable.Moreover, the application of excessive pressure can occlude theunderlying artery, resulting in ischemia and/or thrombosis. Even afterhemostasis has apparently been achieved, the patient must remainimmobile and under observation for hours to prevent dislodgment of theclot and to assure that bleeding from the puncture wound does notresume. Renewed bleeding through the tissue tract is not uncommon andcan result in hematoma, pseudoaneurisms, and arteriovenous fistulas.Such complications may require blood transfusion, surgical intervention,or other corrective procedures. The risk of these complicationsincreases with the use of larger sheath sizes, which are frequentlynecessary in interventional procedures, and when the patient isanticoagulated with heparin or other drugs.

In recent years, several hemostasis techniques have been proposed toaddress the problem of sealing vessel wall punctures followingpercutaneous transcatheter procedures. Related prior art is described inU.S. Pat. Nos. 5,320,639; 5,370,660; 5,437,631; 5,591,205; 5,830,130;5,868,778; 5,948,425; 6,017,359; and 6,090,130. In each of thesepatents, bioabsorbable, thrombogenic plugs comprising collagen and othermaterials are placed proximal to the vessel wall puncture site to stopbleeding. The large hemostasis plug stimulates blood coagulation in thevessel puncture site, but blocks the catheter entry tract, makingcatheter reentry more difficult, if required.

Other related prior art disclosed in U.S. Pat. Nos. 5,707,393;5,810,884; 5,649,959; and 5,350,399 provides for the use of smalldissolvable disks or anchors that are placed in the vessel to block orclamp the puncture hole. However, any device remaining in the vessellumen increases the risk of thrombus formation. Such a device also candetach and cause occlusion in a distal blood vessel, which would likelyrequire major surgery to remove.

Additional prior art includes U.S. Pat. Nos. 5,779,719; 5,496,332;5,810,850; and 5,868,762. In the disclosure of these patents, needlesand sutures delivered through catheters are used to ligate the puncture.The suturing procedure requires particular skill. Suture material leftin the vessel may cause tissue irritation that will prolong the healingprocess.

Still other prior art is disclosed in U.S. Pat. No. 5,626,601, wherein aprocoagulant is injected into the puncture, with a balloon catheterblocking inside the vessel lumen. However, in some cases, the clottingagent may leak past the balloon into the vessel lumen and causestenosis.

Yet other prior art references related to this topic include U.S. Pat.Nos. 4,929,246; 5,810,810; and 5,415,657, which disclose the use of alaser or of radio-frequency (RF) energy that is transmitted to the bloodvessel through a catheter to thermally fuse or weld the punctured tissuetogether.

All of the above cited prior art references require either introducingand leaving foreign objects in the patient's body, and/or inserting atubular probe of large diameter into the tissue channel left by thecatheter in order to seal the puncture.

As will be evident from the preceding discussion, there is a clear needfor an improved method and apparatus for sealing a puncture left in ablood vessel, following an intravascular catheterization procedure. Themethod and apparatus should cause rapid cessation of bleeding, not relyon blood clot formation, and should be independent of the patient'scoagulation status. By employing such a method and apparatus, thepatient will be more comfortable as a result of shortened hemostasis andambulation times, and physician and hospital resources will thereby beminimized. In addition, the method and apparatus should not leave anyforeign object in the patient's body, to reduce the risk of stenosis ator distal to the puncture wound. An ideal device will be noninvasive andshould not include any component that must be inserted in the cathetertract and which might further damage the wound and impede the sealingprocess.

SUMMARY OF THE INVENTION

In accord with the present invention, a method and apparatus are definedthat provide advantageous solutions to the problem of expeditiously andsafely sealing vascular catheter entry wounds made in connection withmedical procedures. The method includes the steps of determining a siteof the puncture in the vascular vessel and positioning an ultrasonictransducer applicator at a position adjacent to the site. The ultrasonictransducer applicator is coupled to a control that includes a processorprogrammed to administer ultrasonic energy in a manner thatefficaciously seals a puncture. A user is enabled to initiate a processthat is controlled by the control, so that very little operator trainingis required. The control automatically controls the ultrasonictransducer applicator so that the ultrasonic energy produced by theultrasonic transducer applicator is focused at the site and isadministered at a sufficient intensity and duration to denature tissueat the puncture, closing and sealing the puncture.

To determine the site of the puncture, an imaging ultrasonic beam isgenerated with the ultrasonic transducer applicator and is transmittedinto the patient, proximate an expected location for the site. Areflection of the imaging ultrasonic beam is then received from withinthe patient using the ultrasonic transducer applicator, producing acorresponding output signal. The output signal is processed with theprocessor included in the control to facilitate determining the site ofthe puncture.

For example, a visual indication of a location of the site of thepuncture can be provided to enable an operator to position theultrasonic transducer applicator so that the ultrasonic energy producedby the ultrasonic transducer applicator is directed at the site. Such avisual indication may be in the form of, for example, lighted displayindicators. In one form of the present invention, the visual indicationincludes an image of the site in which an axis of the vascular vessel isvisually evident, enabling the operator to position the ultrasonictransducer applicator longitudinally along the axis of the vascularvessel so that the ultrasonic energy is directed at the site of thepuncture.

In an alternative embodiment, an object is provided that extends intothe puncture from outside the patient. The operator can then estimatethe location of the puncture along the longitudinal axis of the vesselbased upon a disposition of the object extending outside the patient. Asyet a further alternative, the visual indication includes an image ofthe site in which the object extending into the puncture is evident. Anestimate is made of the location of the puncture based upon adisposition of the object in the image.

Finally, the output signal can be processed with the processor todetermine the site of the puncture. An indicator disposed on theultrasonic transducer applicator can be controlled by the processor toprovide an indication of a direction in which the ultrasonic transducerapplicator should be moved to position it adjacent to the site of thepuncture.

The processor is preferably used for automatically controlling at leastone of a direction, an intensity, and a focus of the ultrasonic energy,to ensure that the ultrasonic energy is administered to the site of thepuncture. Using the processor, the ultrasonic energy is directed so asto overscan the site of the puncture, ensuring that the puncture isclosed and sealed. For example, the processor can move the focus of theultrasonic energy while it is being administered, to overscan the siteof the puncture. As another alternative, an ultrasound emitter of theultrasonic transducer applicator has an aspheric shape so that theultrasonic energy that is directed at the site of the puncture covers alarger area that overscans the site. Other transducer configurationsthat provide a laterally broadened focal region may also be employed.

Preferably, the ultrasonic transducer applicator uses a common array oftransducers for generating both the imaging ultrasound beam and theultrasound energy that closes and seals the puncture.

It is also contemplated that the administration of the ultrasonic energybe interrupted, to again generate the imaging ultrasound beam, therebyconfirming whether the ultrasonic energy is being directed at the siteof the puncture.

The processor is preferably employed to control a force applied againsta surface of the patient using a force generator included in theultrasonic transducer applicator. This force is controlled so that apressure developed by the force is sufficient to substantially stopfluid leakage from the vascular vessel, but not so great as tosubstantially occlude fluid flow through the vascular vessel.

Another aspect of the invention is directed to enclosing the unitapplicator within a protective, acoustic coupling shell. The protective,acoustic coupling shell is adapted to contact an external dermal portionof the patient in order to convey the ultrasonic energy transdermally tothe site of the puncture, while isolating an ultrasonic emitter surfaceon the ultrasonic transducer from direct, contacting exposure to thepatient. The protective, acoustic coupling shell is preferablypre-sterilized and preferably includes a gel patch on an outer surfacethat is protected by a tab. The tab is removed prior to contacting theexternal dermal surface of the patient.

Still another aspect of the present invention is directed to apparatus.The apparatus include elements that carry out functions generallyconsistent with the steps of the method discussed above.

BRIEF DESCRIPTION OF THE DRAWING FIGURES

The foregoing aspects and many of the attendant advantages of thisinvention will become more readily appreciated as the same becomesbetter understood by reference to the following detailed description,when taken in conjunction with the accompanying drawings, wherein:

FIG. 1 is a schematic block diagram of the primary components employedin a preferred embodiment of the present invention;

FIG. 2 is a schematic diagram illustrating how the present invention isemployed for sealing a puncture in a vessel;

FIG. 3 schematically illustrates a collagen seal produced by the presentinvention to close the puncture in the vessel of FIG. 2;

FIG. 4 is a flow chart illustrating the logical steps followed duringsealing of a vascular wound in accord with the present invention;

FIG. 4A is a flow chart illustrating the optional steps employed fordetecting nerves during the method of FIG. 4;

FIG. 5 is a cross-sectional view of a portion of a patient's body,illustrating an applicator unit in accord with the present inventiondisposed adjacent to a puncture that extends transdermally into anartery;

FIG. 6 is a cutaway isometric view of the applicator shown in FIG. 5;

FIG. 6A is an isometric view showing the force sensing transducer, forcegenerator, and ultrasonic array of the applicator;

FIG. 7 is an elevational view of a locator rod adapted to be insertedinto a puncture wound over a guide wire;

FIG. 7A is a cross-sectional view of a portion of a patient's body likethat in FIG. 5, illustrating the locator rod of FIG. 7 being used todetermine a location of a puncture in the artery relative to theapplicator unit;

FIG. 7B is similar to FIG. 7A, but illustrates the use of ultrasonicpulse-echo techniques to determine the spatial location of the locatorrod;

FIG. 7C depicts a view of a framed two-dimensional image a target regiongenerally orthogonal to that shown in FIG. 7A and FIG. 7B, for use inlocating the puncture site;

FIG. 8 is a schematic isometric view of an embodiment of the applicatorthat uses a disposable shell;

FIG. 8A is an side view of the disposable shell of FIG. 8;

FIG. 9 is a schematic system block diagram depicting modules included inthe applicator and control unit;

FIGS. 10 and 10A respectively illustrate the ultrasound beam orientationrelative to the vessel from the side of the vessel and as viewed alongthe vessel;

FIG. 11 is a plan view of an embodiment of the applicator illustratingthe controls and indicators that it includes;

FIGS. 12A and 12B respectively illustrate the side and longitudinalgeometry of the therapeutic ultrasound beam; and

FIG. 13 is an isometric view illustrating the ultrasound beam geometryproduced by an aspheric transducer.

DESCRIPTION OF THE PREFERRED EMBODIMENT

Use of Ultrasound for Sealing Punctures

Because of its unique properties in soft tissue, ultrasound can bebrought to a tight focus at a distance from its source. If sufficientenergy is radiated within the ultrasound beam, cells located in thefocal volume can be rapidly heated, while intervening and surroundingtissues are spared. Surrounding tissues are unaffected in the unfocusedportion of the ultrasound beam because the energy is spread over acorrespondingly larger area and associated heating is minimized.

Whereas ultrasound intensities on the order of 0.1 Watts/cm² areemployed in diagnostic imaging applications, intensities in excess of1,000 Watts/cm² are typical in high-intensity focused ultrasound (HIFU)applications. At the focal point, these high intensities result inlarge, controlled temperature rises within a matter of seconds.

It has been demonstrated in numerous in vivo animal studies that HIFUcan rapidly seal blood vessel punctures and lacerations over a widerange of sizes. When accurately targeted on a vascular wound, ultrasoundhas been shown to induce complete hemostasis in less than one minute inthe femoral, carotid, and axillary arteries, and in the femoral andjugular veins of large animals, while blood flow through the treatedvessels remained unaffected. These investigations included: (a) sealingpunctured, surgically exposed vessels using visual targeting, (b)sealing incised, surgically exposed vessels using visual targeting, (c)sealing surgically exposed, punctured vessels using Doppler-guidedultrasound targeting, and (d) noninvasive sealing of punctured vesselsunder ultrasound imaging guidance wherein complete hemostasis was notedin 13±12 seconds.

The mechanism of hemostasis in these ultrasound-exposed vascular woundsappears thermal in origin and involves denaturization of nativeperivascular collagen with subsequent formation of an extensive fibrinnetwork that covers the hole, thereby sealing it closed. The fibrinlinks with adjacent vessel wall tissues to form a seal that has beenshown to be independent of puncture hole size. Acoustic streaming forcesgenerated by the HIFU beam were also observed to play a role in opposingthe escape of blood from the vascular wound. Blood clotting is notbelieved to be a factor in achieving acoustic hemostasis, as evidencedby equally rapid and complete wound sealing in highly anticoagulatedanimals and in ex vivo vessels in which saline has been substituted forblood.

Overview of the Present Invention

FIGS. 1 and 2 show the main components of an ultrasonic system suitablefor use in implementing the present invention. As illustrated in FIG. 1,a hand-held applicator unit 2 is positioned over an arterial wound 8 inthe patient. Included with the hand-held applicator unit is a generallysingle-use, pre-sterilized cover and acoustic coupling shell 4 thatslips over applicator 2. A control unit 6 implements algorithms tofacilitate the method and is coupled to applicator 2.

The user enters various conventional scan and control parameters into aninput unit 70, which typically includes user input devices 72. Examplesof such devices include a keyboard, knobs, and buttons. The input unitis connected to a processing system 74, which will typically comprise aplurality of microprocessors and/or digital signal processors.Processing system 74 may, however, also be implemented using a singleprocessor of sufficient speed to handle the various tasks describedbelow. A conventional memory 75 will normally be included in the systemto store, among other data, transmission control parameters and imagingdata generated in any given implementation of the present invention.

Processing system 74 sets, adjusts, and monitors the operatingparameters of a conventional transmission and control circuit 76.Control circuit 76 forms a transmit ultrasonic waveform by generatingand applying electrical control and driving signals to an ultrasoundtransducer 78, which preferably comprises an array of individuallycontrollable piezoelectric elements. As is well known in the art, thepiezoelectric elements generate ultrasonic waves when electric, signalsof a proper frequency are applied to them; conversely, when receivingreflected ultrasonic waves, they generate electrical signalscorresponding to the mechanical vibrations caused by the returningultrasonic waves.

Transducer 78 is positioned against it portion 82 of the body of apatient, and by varying the phasing, amplitude, and timing of thedriving signals for the transducer array elements, ultrasonic waves arefocused to form a transmit beam 314 of high-intensity ultrasound.

In FIG. 2, open arrows indicate the direction of a flow of blood withina blood vessel 312, which has a puncture site 316 that may have beencaused by introduction of a catheter or, in the case of unintendedpunctures that have produced wounds, by some other object. The tissueforming a layer 318 of collagen found on the surface of blood vessels isalso shown in FIG. 2 surrounding blood vessel 312.

As will be clear from the description of the present invention below, itis not necessary for the system to include an imaging capability.However, the provision of an imaging capability, including pulse-echolines of interrogation that are not displayed as images, in the presentinvention should assist a user to more accurately locate a vascularpuncture site. It is recognized that a full display of the insonifiedvascular target site is not required.

Nonetheless, since imaging of a vascular target site is preferable andwill employ echo processing (especially, Doppler), FIG. 2 alsoillustrates a reception controller 88, which will include conventionalamplification and signal conditioning circuitry as needed. Receptioncontroller 88, all or part of which is normally integrated intoprocessing system 74, converts the ultrasonic echo signals (which aretypically at radio frequencies, on the order of a few to tens ofmegahertz) into lower frequency ranges for processing and may alsoinclude analog-to-digital conversion circuitry. The processing includes,as needed, such known signal conditioning as time-gating, gaincompensation, Doppler frequency shift processing, and diffractioncompensation, in order to identify echo signals from any selected focalregion. The type of conventional signal processing needed (if any) willin general depend on the particular implementation of the presentinvention employed and can be implemented using known design methods.

Note that it is not essential, according to the present invention, thatthe transducer 78 be used externally, relative to the patient's body. Itis also contemplated that the transducer may be maneuvered inside apatient's body, and the beam focused on a puncture from inside the body.For example, a transesophageal probe, laparoscopic, or other probeinserted into a body cavity, such as the vagina or rectum can be used topractice the present invention. A suitably designed probe inserted intoan open body cavity or via minimally invasive means could be used toarrest bleeding in surgical or trauma care situations. Yet, most of thefollowing discussion is directed to a preferred embodiment of thepresent invention in which the transducer is intended to be usedexternally, since an initial commercial product in accord with thepresent invention will be designed for such use.

A conventional display system 92 may also be included in order todisplay information concerning transmission power, time, focus data,etc. The display system will include known circuitry for scan conversionand for driving the display, as needed. These circuits are well knownand therefore need not be specifically illustrated or described furtherto provide an enabling disclosure.

FIG. 3 illustrates the result of an insonification of puncture site 316using the present invention. As the focal point of transmit beam 314(see FIG. 2) is moved around (as illustrated by the arrows pointing ineither direction from the focus of the beam) the area of puncture site316 using conventional beam-steering techniques, the tissue adjacent thepuncture site 316 will denature. In effect, the collagen in the tissue“melts” and flows over and into the puncture opening. When the collagencools, it forms a “patch” that not only covers the puncture, but alsoflows partially into the puncture opening in the wall of the bloodvessel. Moreover, since the denatured tissue tends to contract, it alsotends to pull the edges of the puncture together and thus further closethe wound.

It should be noted that the present invention can be employed to sealvascular wounds of various types and is not limited to the type of woundcreated as a result of interventional procedures in which a catheter hasbeen introduced into a vascular vessel. As noted above, application ofthermal treatment to the tissue overlying a wound has been demonstratedto seal the wound. In the present invention, a practical method has beendeveloped for repeatedly and reliably achieving sealing of the puncturein a vascular vessel. Steps carried out in this method are shown in FIG.4, which is discussed below. These steps represent one preferredembodiment of the present invention, but do not represent allalternatives that might be employed to achieve acceptable sealing.

Key steps in the method for vascular sealing described here include:

-   -   1. Positioning an ultrasound generating source on a patient such        that the source is targeted at an area including the wound to be        sealed;    -   2. Applying a pressure against the patient in an area overlying        the wound and directed substantially toward the vessel to be        treated;    -   3. While the pressure and the positioning of the ultrasound        source are maintained, carrying out an insonification of a        volume of tissue that includes the wound, using an ultrasound        exposure that delivers an acoustic energy density (measured at        the approximate location of the wound), in excess of 100        joules/sq. cm, but generally less than several thousand        joules/sq. cm.        Additional steps of the method described below employ the        apparatus in an automated manner that facilitates ease of use        and ensures the safety and consistency of the results obtained.

A clinically acceptable device for sealing a puncture wound in accordwith the present invention must meet a number of requirements,including:

-   -   1. The device and associated procedure must be safe to use in        that they avoid undesirable bioeffects, so that the patient is        not injured directly or indirectly as a result of the procedure;        also, in the event that effective vessel sealing does not occur        as desired, traditional methods of applying pressure to the        wound are sufficient to accomplish hemostasis;    -   2. The device and associated procedure must be easy to use in an        efficient manner, to facilitate proper, repeatable execution of        the sealing process; requirements for operator training should        be minimized;    -   3. The sealing process must be sufficiently fast to enable the        entire procedure to be rapidly completed—preferably, in less        than 5 minutes;    -   4. The cost per sealing procedure should be minimized; and,    -   5. The efficacy of the device should be very high, generally        achieving a success rate in excess of about 95%; acceptability        of the present invention in routine clinical practice does not        permit an unpredictable outcome.

These requirements are met by the present invention, as described below,and as defined in the claims that follow. A preferred embodiment of thedevice includes the components shown in FIGS. 1 and 2, which weredescribed above.

FIG. 6 and FIG. 6A show one preferred embodiment of applicator unit 2.The applicator unit includes an outer housing 10 having an ergonomicallyconsidered shape so that it can be conveniently hand held. The outerhousing is best fabricated from an injection moldable plastic materialsuch as ABS or the like. The operator grasps the outer housing of theapplicator unit so as to enable a control push-button 14 to beaccessible and indicators 12, 16 and 30, 32, 34, and 36 to be visible tothe operator. Positioning the applicator unit at the appropriatelocation over the wound area and activation of an essentially automatedtreatment cycle are readily accomplished. The operator simply refers tothe indicators to determine when the applicator unit is properlypositioned and ready for use. Indicators 12 and 16 are used to indicatewhen alignment of the applicator unit with the longitudinal axis of thevessel to be sealed has been achieved. Indicators 30, 32, 34, and 36display the state of operation and instruct the operator with respect toholding the applicator in place as described in detail later in thisdescription. Control 14 when pressed, activates the treatment cycle,thus initiating a sequence of operations that determine ultrasonic scanparameters (exposure time, scan pattern, intensity, focal range, etc.).

As shown in FIG. 6A, ultrasonic array assembly 20 is held within outerhousing 10 on a shaft 40, in a bearing assembly within a forcetransducer 18, so as to permit movement of the ultrasonic array assemblyto and away from patient 8. Shaft 40 passes through the bearing assemblyprovided within a force generator 18 and terminates at a contactingforce sensing transducer 42. Force generator 18 comprises anelectromagnetic solenoid that is rigidly supported and mounted withinhousing 10 by structural members 46. The face of ultrasonic arrayassembly 20 is in contact with the appropriate location on the body ofthe patient (overlying the site of the puncture) and is thus capable ofapplying a substantially compressive, controllable force on the tissuestructures with which it is in contact. The force applied by theultrasonic array assembly is produced at least in part by controllablyenergizing force generator 18. Ultrasonic array assembly 20 preferablyoperates in a multiplicity of modes; however, separate ultrasonictransducers can instead be provided for some or all of the functionsperformed in a different design within the scope of the presentinvention.

In the illustrated preferred embodiment, electrical connectionscomprising wires 26 are routed within the outer housing 10 and out in asealed bushing 44 that mounts a cable 28 to the control unit 6. Cable 28is sufficiently long, on the order of 10 feet in length, so that thecontrol unit may be conveniently located at a distance from the patientand operator location.

Applicator unit housing 10 is shaped to be used with a slip-on,generally single-use protective applicator shell 4 (illustratedschematically in FIG. 1). The shell employed in the preferred embodimentis shown in greater detail in FIGS. 8 and 8A. Shell 4 has side walls 54that are fabricated from a generally optically transparent, semi-rigidplastic material. A skirt 52 extends from the rear of the shell and ispleated so that in preparing for use of the applicator unit, an operatorcan grasp the skirt and extend it sufficiently to protect a sterile areaof the patient from coming into contact with cord. The protective shellis packaged in a sterile condition. The shell is fabricated from aflexible plastic material having low acoustic absorptioncharacteristics. A fiducial mark 56 is provided on a side of theapplicator unit and visible through the optically transparent materialof the protective shell. This fiducial mark is employed to visuallyalign the applicator unit with a position on the patient at which theapplicator unit will be used to seal a puncture.

Sterile, generally gas free acoustic coupling gel 62 is deposited in apatch on the bottom of flexible bottom 58. Prior to use, the gel is heldin place and sealed by semi-sticky adhesive coated tab 60. Tab 60 isremoved by the operator just prior to use, thereby exposing the gel sothat it provides a good acoustic coupling with the surface of thepatient's body. Protective applicator shell 4 thus provides a sterilebarrier over the multi-use applicator unit and conveniently provides apre-determined amount of a specific appropriate acoustic couplingmedium. Although not shown, it is contemplated that the bottom of theinterior cavity of the shell may also include a layer of acousticcoupling gel to ensure good acoustic coupling between the applicatorunit through the protective, applicator coupling shell.

With reference to FIG. 1, applicator unit 2 is connected to control unit6. Power supplies, signal processing components, and control and RFpower generation components are housed within control unit 6. FIG. 9 isa system block diagram illustrating the modules disposed, in thepreferred embodiment, within the applicator unit 2 (i.e., the componentshown within the dotted line portion of this Figure) as well as themodules (all other modules that are not in the applicator unit) disposedin the control unit 6. In this preferred embodiment, control unit 6 ispackaged in a small, self-contained pole- or cart-mounted enclosure thatderives its input power from a standard AC line power service (notshown). Power supplies with the unit are designed to assure low leakagecurrents for patient safe operation.

In the preferred embodiment the architecture of control unit 6 is basedon a programmable processing unit which processes various signals andcontrols a number of functional modules. A microprocessor is well suitedto perform the computation and control functions required. Applicatorunit 2 is coupled to control unit 6 by a plurality of signal paths 212,214, 216, and 218. Signal path 212 couples display drivers 200, whichare controlled by a computer/controller 236, with indicators 30, 32, 34,and 36 on the applicator unit. Control button 14 on the applicator unitis coupled through signal line 214 to an interface 202 and thus to thecomputer/controller. Force sensing transducer 42 produces an outputsignal indicative of the force (i.e., the pressure) applied against thesurface of the patient's tissues by the applicator unit, and this signalis conveyed by signal lines 216 to an interface 204, which provides thesignal to the computer/controller. In response to the magnitude of themonitored force, the computer/controller produces a control signalapplied to a driver 206, which provides the current signal used toenergize force transducer 16, to determine any additional force that itgenerates to achieve a desired pressure on the site of the puncture thatis sufficient to prevent loss of fluid from the vessel, but not so greatas to occlude the flow of fluid through the vessel.

Signal lines 240 couple ultrasonic array assembly 20 to atransmit/receive switch 224. The transmit/receive switch determines theoperational mode of the ultrasonic array assembly under the control ofthe computer/controller. When operating in a diagnostic mode in whichthe ultrasonic array assembly is producing an imaging ultrasound beam,the signal corresponding to the echo reflected received by ultrasonicarray assembly 20 from tissue and other structures is conveyed throughtransmit/receive switch 224 and through signal lines 222 to an amplifierdigitizer array 220. The output signals from the amplifier digitizerarray are conveyed to computer/controller 236 through signal lines 228.When the ultrasonic array assembly is generating either the imaging beamor the HIFU beam, it is responding to signals received from an RFgenerator 232 that is coupled to a phase shift/amplifier array 234 bysignal lines 236, and to a control signal provided by thecomputer/controller and conveyed to the phase shift/amplifier on asignal line 230. The output of the phase shift/amplifier is conveyed onsignal lines 226 to transmit/receive switch 224, and thus, to ultrasonicarray assembly 20 through signal lines 240. Manual control inputs 241are coupled to computer/controller 236 through signal lines 242.

A number of variously advantageous transducer configurations mayalternatively be employed in this invention. Possibilities include:

-   -   Configurations wherein therapeutic and, pulse-echo Doppler        functionality are accomplished by the same ultrasonic transducer        or by separate ultrasonic transducers; and,    -   Configurations wherein the ultrasonic transducer is either of a        fixed focus type, or a segmented electrically selectable macro        element array, or a phased array, or a linear array, or an        annular array; and,    -   Configurations where a large focal spot 412 (see FIG. 13) (e.g.        a focal spot produced by a transducer having an aspheric shape),        or those in which a tightly focused spot is produced; and,    -   Configurations wherein the ultrasonic transducer is mechanically        positioned (or scanned), or those in which it is fixed in one        position.

An aspheric ultrasonic transducer configuration has the advantage ofcovering a large treatment area on the surface of the vessel without thecomplication of electronic or mechanical beam steering. Covering a largearea (i.e., overscanning) is desired in order to ensure that the actualsite of the puncture wound is treated, given its positional ambiguity.FIG. 13 depicts the geometry of such a configuration. In thisembodiment, an ultrasonic transducer 404, excited by an appropriate RFsource via connections 402, is generally aspheric in shape and does notbring the ultrasound beam to a sharp focus. The ultrasonic energy thatit produces covers area 412 on a vessel 408 that includes puncture wound410. Fluid or solid material acoustic coupling (not shown) is usedbetween the ultrasonic transducer and the tissues of the patient.

In one preferred embodiment, the method described includes a series ofmanual steps (operator actions) and automated steps. The automated stepsare carried out as control processes or algorithms executed by one ormore processors and other hardware in accord with machine instructionsexecuted by the one or more processors. It is understood that variationsin the order of these steps, and in the total complement of stepsimplemented is possible in alternative embodiments. Steps as shown inFIG. 4 are described as follows.

In a step 100 labeled Patient Preparation, the operator positions thepatient and the apparatus so that the applicator unit is convenientlypositioned over the puncture wound area, e.g., over the puncture made bya catheter in the femoral artery. Shell 4 is removed from its sterilepackage and fitted onto applicator unit 2, and gel sealing tab 60 (shownin FIGS. 8 and 8A) is removed, exposing the gel 62.

A step 102 labeled Manually Align is then carried out. With the catheterintroducer in the wound, the operator palpates the area locating thepoint at which the introducer just enters the artery. The operator marksthis location on the patient's skin with a suitable marking device (e.g.a surgical marker), drawing a line substantially perpendicular to theperceived direction of the artery, extending approximately 3 cm from theentry wound location. It is the purpose of this marking to estimate thelongitudinal location of the wound; the operation of the HIFU sealingprocess provides for an overscan of the wound area so that practicalvariations in the operator's ability to make the longitudinal positionestimate are permissible. Other techniques for locating the site of thepuncture are discussed below. In a more preferred embodiment, lateraland range locations of the wound are more precisely located by theautomated capability of the processor(s) used in the apparatus.

Also within step 102, the operator places the device over the woundlocation, aligning fiducial mark “56” (shown in FIG. 8) with the linethat was drawn on the patient's skin. The applicator unit is rotated inplace until both alignment indicators 12 and 16 (FIGS. 6 and 8)illuminate, indicating that the artery is axially aligned under theapplicator unit.

The axial alignment indications are, in this preferred embodiment,derived from two ultrasonic pulsed Doppler interrogations. FIGS. 10 and10A show the geometry of the Doppler alignment beams. Use of aultrasonic transducer 20 enables the same ultrasonic transducer to beemployed to produce an imaging beam and the HIFU beam for both apulse-echo targeting mode and a therapeutic mode.

In the alignment sequence illustrated in FIGS. 10 and 10A, phased arrayultrasonic transducer 20 sends and receives a downstream pulsed Dopplerline 304 and an upstream line 308 sequentially. Lines 304 and 308 are inplane with the axial centerline of the applicator unit and a lineperpendicular to the bottom surface of the applicator unit. Lines 304and 308 are transmitted at angles A and B with respect to a line 306,which is perpendicular to the applicator unit. Angles A and B are chosento provide a axial separation as well as an appreciable vector flowcomponent in the direction of the interrogating line—an angle ofapproximately 45 degrees. Direction of flow in an interior 310 of thevessel is sensed and tested to assure that an artery 300 (not a vein) isbeing interrogated. Doppler signals, from lines 304 and 308, integratedover an appropriate range, above a pre-determined threshold value, areused to cause the illumination of alignment indicators 12 and 16respectively. Averaging multiple lines is, in this preferred embodiment,employed to improve the performance of the alignment detection scheme.The conditioned signals also set logical flags so that the system mayinterlock the initiation of a therapeutic treatment sequence withassurance of alignment. Thus in a decision step 106 (FIG. 4), alignmentis tested by interrogating the logical presence of both of the flags.

Alternatively, another advantageous configuration for guiding the manualalignment process uses multiple Doppler lines and multiple indicators,with reference to FIG. 11, which illustrates a top view of theapplicator unit. In this configuration, three parallel lines aretransmitted and received in the two directions indicated by lines 304and 308 in FIG. 10. Additional transducers are appropriately positionedin housing 10 (FIG. 6). Pulsed Doppler signals are processed in a mannersimilar to that described above. Thus, for example (referring to FIG.11), if the alignment is off-center and rotated to the left, indicatorlights 336 and 334 would be illuminated, indicating the misalignment andsuggesting the appropriate direction to move the applicator unit toachieve alignment (denoted when indicators 338 and 330 are illuminated).Alternatively, continuous wave Doppler may be employed to interrogatethe flow position of the target artery, with operation essentiallysimilar to that described above.

With verified alignment in step 106. the system proceeds to a step 108labeled Set Pressure, wherein the pressure over the artery is set andcontrolled within a predetermined range using force generator 18 (FIG.6) and force sensing transducer 42. In this preferred embodiment, theweight of the applicator unit is purposefully made to be in a rangewhere additional pressure applied by the operator to hold the unitfirmly in place is reduced. This useful weight is about 1 lb (0.45 kg)or more. Force generator 18 is activated and controlled such thatapplied pressure to the artery partially restricts flow, but maintainssufficient flow so that thermal cooling due to blood flow within theartery protects the intimal lining of the vessel from irreversibledamage. Presence of a Doppler flow signal on down-stream line 304 (FIG.10) is employed to assure vessel patency.

In this preferred embodiment, when the system has completed the pressureapplication cycle described above, indicator 32 (FIG. 6), which ismarked “READY” on the applicator unit is illuminated (see block 118 FIG.4), indicating to the operator that a treatment cycle may be manuallyinitiated (triggered) by pushing control button 14. The system is in await state as indicated in a decision block 112 in FIG. 4, until amanually triggered treatment cycle is detected. With the detection of atriggered treatment cycle, axial alignment is verified in a step 114 bygenerally repeating the logical test described at step 102.

A step 116 then makes a ranging measurement to estimate the acousticpath length between ultrasonic transducer assembly 20 and the vesselboundary. i.e. the distance between points F and C along line 306 inFIG. 10. Pulsed Doppler is, in this preferred embodiment, employed tomake this measurement, wherein lines 304 and 308 measure distances F-Dand F-E, respectively. Points D and E are recognized by the fact thatthese correspond to the first instance of flow detected along each lineas range increases. The range estimate of FC is therefore:FC˜(FE COS A+FD COS B)/2  Equation 1

A step 120 estimates the acoustic attenuation at the therapeuticfrequency between ultrasonic transducer assembly 20 and the targetcollagen layer overlaying the vascular wound, path F-C in FIG. 10. Inthis preferred embodiment, a simplified approach is employed whereinestimated dimension FC is used to access data in a look-up table ofattenuation values. Attenuation values in the table are predetermined byempirical measurement. Alternatively, more sophisticated A-Modeattenuation measurements may be employed to assess to F-C path.

A step 122 determines the therapeutic ultrasound exposure parameters tobe employed. Dimension F-C, the attenuation estimate, and optionally,patient parameters (e.g., size and weight), input at module 240 in FIG.9, are used to access predetermined data and scan protocols in residentlook-up tables Ultrasound scan geometry, intensity and epochal exposureintervals are thus determined.

Ultrasound scan geometry, intensity and time parameters are determinedto accomplish three key objectives: (1) provide a sufficient overscan ofa longitudinal and lateral surface of the target vessel so as to includethe site of the wound; (2) ensure delivery of an appropriate energy doseto the collagen layer in the region of the target site to raise itstemperature to a range of between 60 and 100 degrees Celsius for apredetermined period of time; and, (3) assure that the skin andinterpath tissue is not exposed to a temperature-time exposure that willresult in pain and or irreversible tissue damage.

Therapeutic scan geometry is shown in FIGS. 12A and 12B. A therapeuticlevel of approximately 50 watts total transmitted acoustic power,generally weakly focused, is transmitted along a centerline 314 througha dermal layer 302. The desired scan pattern is achieved by directingthe beam over varying angles of the beam with respect to a line 320 thatextends perpendicular to the center of the face of the application unit.Thus, for example, a raster scan pattern may cover a therapeutic area,over collagen layer 318, of dimensions 1 cm wide by 1.5 cm long (in thearterial axial direction). Such an overscan of the wound site providesfor variations in the operator's ability to predetermine and locate theprecise lateral position of the wound, as well as the variation in woundlocation that results from the possible variation of wound lateral entrypoints. Importantly, scan geometry is selected such that ultrasonicexposure is generally confined to the vessel, minimizing the possibilitythat an adjacent vein or nerve structure will be insonified.

A step 126 carries out the therapeutic exposure cycle. It is generallydesirable to hold the applicator unit in place, providing theestablished orientation and pressure for a period of time after thetherapeutic exposure cycle. A hold interval 130 (FIG. 4) is selected toenable exposed tissue structures to cool, a time period of approximately1 minute. Following this time period, indicator 36 on the applicationunit (FIG. 6) marked “COMPLETE” is illuminated and the “HOLD” indicatoris turned off, instructing the operator that the therapeutic treatmentis completed and the device may be removed from the patient.

In situations where there is concern for inadvertent exposure of a nervestructure, an additional sequence depicted in FIG. 4A may optionally beemployed. The sequence is inserted into the process flow of FIG. 4, inthis preferred embodiment, at a location marked “A.” To detect thepresence of a nerve structure, a weak, sub-therapeutic energy levelultrasonic pulse is transmitted in a step 136 (FIG. 4A), to cover thedetermined target area. The operator observes in a decision step 138whether a reaction of pain and or uncommanded movement from the patienthas occurred, indicating that a nerve structure has been stimulated.System logic then waits for an addition manually initiated trigger inputin steps 140 and 142, prior to proceeding with therapeutic exposure atstep 126 in FIG. 4.

Alternative Techniques for Aligning the Applicator Unit

Step 102, which facilitates alignment of the applicator unit over thewound area and targeting of the therapeutic exposure, may beaccomplished using several alternative approaches compared to thatdescribed above. It is desired to employ an approach for targeting andaligning the applicator unit that is easy to implement and requiresminimum operator instruction. The approach further should be consistentwith minimizing bleeding during the process of achieving alignment.Additionally, the approach should be robust and provide targeting of.the wound site with sufficient accuracy such that the wound willreliably be included within the area of therapeutic exposure.

A principle employed in the present invention is the concept that theoverscan of the target location during therapeutic exposure issufficient to accommodate targeting ambiguity and possible patient oroperator movement during the procedure. Nevertheless, accurate targetingis needed to ensure efficacy of the wound sealing process.

In the preferred embodiment described above, pulsed Doppler ranging wasemployed to locate the axis of the vessel, and the operator was advisedof the longitudinal location of the wound on the vessel by reference tovisual landmarks on the skin surface. Alternatively, by inclusion ofadditional automation, the need for the operator to locate thelongitudinal position is eliminated, thereby substantially simplifyingthe targeting procedure for the operator.

These alternative approaches make use of the entry channel along whichthe introducer and guide wire are commonly passed during diagnostic andinterventional catheterization procedures. FIG. 5 illustrates thegeometry that relates the location of applicator unit 2 to the locationsof an entry channel 518 and a vessel wound 516. In FIG. 5, applicatorunit 2 is positioned on a patient's skin surface 510 over a vessel 506in which a blood flow 508 is contained. A location “C” is indicated atwound 516; a line 512 passes from “C” through entry channel 518,intersecting a plane 514 defined by reference locations on applicatorunit 2 at a point “H.” A point “F” is a reference point in plane 514. Ifthe spatial location of line 512 is known relative to plane 514 andpoint “F,” and the vector distances “H” to “F”, or “C” to “F” are known,then the location of wound 516 relative to applicator unit 2 isdeterminable by basic geometry. Knowledge of this geometry permitsautomated system function to be employed to provide guidanceinstructions (e.g. visual indicators) to the operator during the manualalignment portion of the procedure.

A sufficient number of the parameters in the above described geometrymay be determined by several novel methods and their associatedapparatus. As previously described, acoustic pulsed Doppler may beemployed to determine the distance “C”-“F” (reference FIG. 5). In manyapplications of the vascular sealing method described herein, the vesselis an artery having a substantial high velocity flow and is thus readilylocalized using well known pulsed Doppler techniques. Knowing thisdistance, localization of wound 516 on the vessel is made possible bydetermining the spatial position of line 512.

The spatial location of line 512 may be determined by employing asubstantially rigid, straight locator rod 554 as depicted in FIG. 7,which is placed in entry channel 518. Locator rod may have alongitudinal center bore 556 through which a guide wire 552 may pass. Inpractical use, the introducer used in conjunction with a clinicalprocedure would be removed without removing the guide wire. Locator rod554 would be introduced into the wound over the guide wire. Sealingassembly 550 is disposed at one end of the locator rod to prevent theloss of blood through center bore 556.

Several alternative approaches may be employed to determine the spatiallocation of the longitudinal axis of locator rod 554 and thus, todetermine precise wound location as described above. These approachesinclude:

-   -   1. As shown in FIG. 7A, a spatial position resolving element 558        may be included on locator rod 554. Spatial position resolving        element 558 may be an acoustic position sensor, an optical        position sensor, a magnetic position sensor, an        electromechanical positioning or resolving arm, or an inertial        position sensor. The spatial relationship between the position        of locator rod 554 and applicator unit 2 is accomplished by        either a direct mechanical linkage or by way of an intermediate        electronic or computational circuit.    -   2. As shown in FIG. 7B, an ultrasonic pulse-echo technique may        be employed to determine the spatial location of locator rod        554. A transducer in applicator unit 2 transmits directed        acoustic pulses in more than one direction, e.g., lines 560,        562, and 564, and echoes from structures in each path are        returned and detected by a pulse-echo receiver included in the        applicator unit, as is well know in the diagnostic ultrasound        art. Locator rod 554 provides reflections that permit making        time of flight measurements of, for example, distances “F”-“J,”        “F”“K,” and “F”“L.” Locator rod 554 may be coated or constructed        of materials chosen to enhance acoustic reflectivity, thus        providing echoes that are readily distinguished from background        clutter. Common guide wires may alternatively be used as locator        rod 554, as these wire structures are typically highly        reflective of ultrasound energy. Alternatively, locator rod 554        may be constructed from materials that enhance reflection at a        harmonic of the interrogating ultrasound pulse, providing        another advantageous method for clearly distinguishing the        echoes from locator rod 554 from those received from surrounding        tissue. Materials or coatings that entrap gas bubbles are, for        example, effective in providing higher harmonic reflection. Echo        enhancing properties may also be incorporated into an introducer        that is then used as the locator rod. Pulsed Doppler may also be        employed to identify and locate the locator rod. In this latter        alternative, the locator rod may be a common introducer. A        strong Doppler shifted reflection will return from the lumen of        the introducer even when blood is not permitted to flow out of        the introducer.    -   3. As indicated in FIG. 7C, two dimensional, or three        dimensional, imaging may also be employed to locate locator rod        554, the guide wire, and ‘the introducer, as well as the vessel.        FIG. 7C depicts a view of a framed two-dimensional image 580 of        the target region generally orthogonal to that shown in FIGS. 7A        and 7B. Distance from the ultrasound source increases toward the        bottom of this depiction. This image is generally representative        of a cross-sectional plane of interrogation located at a line        562 in FIG. 7B. Automated image recognition provided by the        processor may be employed to identify structures including        locator rod 554, imaged as a locator rod structure 586 and        vessel 506, imaged as a vessel structure 584 in this image.        Doppler imaging and color flow mapping may be employed to        increase the recognizablility of relevant features. The        interrogating image plane may be scanned over the region        containing the target. When locator rod structure 586 is        recognized at a location just touching the top surface of vessel        structure 584. the wound target. site has been identified.

Although the present invention has been described in connection with thepreferred form of practicing it, those of ordinary skill in the art willunderstand that many modifications can be made thereto within the scopeof the claims that follow. Accordingly. it is not intended that thescope of the invention in any way be limited by the above description,but instead be determined entirely by reference to the claims thatfollow.

What is claimed is:
 1. A method of non-invasively applying heat to aregion proximate to a blood vessel target, the method comprising:generating an imaging ultrasonic beam adapted to image the blood vesseltarget, the blood vessel target having a puncture site; receiving areflection of the imaging ultrasonic beam and in response producing acorresponding output signal; processing the output signal to identify alocation of a treatment zone proximate an outer wall of the blood vesseltarget; detecting the presence of a nerve structure adjacent to theblood vessel target by applying an ultrasonic pulse to the treatmentzone; applying a therapeutic ultrasound energy beam to the treatmentzone, wherein the ultrasound energy beam is a high intensity focusedultrasound energy beam; and moving the therapeutic ultrasound energybeam to over-scan the treatment zone with therapeutic ultrasonic energy,wherein the imaging ultrasonic beam, the ultrasonic pulse, and thetherapeutic ultrasound energy beam are transcutaneously applied.
 2. Themethod of claim 1, wherein the therapeutic ultrasound energy beam ismovable in a plurality of directions at any given time.
 3. The method ofclaim 1, wherein the therapeutic ultrasound energy beam is applied by anultrasonic transducer applicator.
 4. The method of claim 3, wherein theultrasonic transducer applicator comprises an array of transducers. 5.The method of claim 4, wherein the array of transducers is configured toemit the imaging ultrasonic beam.
 6. The method of claim 1, furthercomprising the step of interrupting the application of the therapeuticultrasound beam to generate a second imaging ultrasonic beam to confirmthat the therapeutic ultrasound beam is being directed to the treatmentzone.
 7. The method of claim 1, wherein the intensity of the ultrasonicpulse is less than about 1,000 Watts per square centimeter.
 8. A methodof non-invasively applying heat to a region proximate to a blood vesseltarget, the method comprising: directing an imaging ultrasonic beamproximate the blood vessel target, the blood vessel target having apuncture site; receiving a reflection of the imaging ultrasonic beam;processing the reflection of the imaging ultrasonic beam to identify alocation of a treatment zone proximate an outer wall of the blood vesseltarget; detecting the presence of a nerve structure adjacent to theblood vessel target by applying an ultrasonic pulse to the treatmentzone; applying a high intensity focused ultrasound beam to the treatmentzone; and moving the high intensity focused ultrasound beam to over-scanthe treatment zone with therapeutic ultrasonic energy, wherein theimaging ultrasonic beam, the ultrasonic pulse, and the therapeuticultrasound energy beam are transcutaneously applied.
 9. The method ofclaim 8, wherein the high intensity focused ultrasound beam is movablein a plurality of directions at any given time.
 10. The method of claim8, wherein the high intensity focused ultrasound beam is applied by anultrasonic transducer applicator.
 11. The method of claim 10, whereinthe ultrasonic transducer applicator comprises an array of transducers.12. The method of claim 11, wherein the array of transducers isconfigured to emit the imaging ultrasonic beam.
 13. The method of claim8, further comprising the step of interrupting the application of thehigh intensity focused ultrasound beam to generate a second imagingultrasonic beam to confirm that the high intensity focused ultrasoundbeam is being directed to the treatment zone.
 14. The method of claim 8,wherein the intensity of the ultrasonic pulse is less than about 1,000Watts per square centimeter.
 15. The method of claim 1, wherein thepresence of the nerve structure is determined based on the pain of apatient in response to the ultrasonic pulse.
 16. The method of claim 1,wherein a direction of the therapeutic ultrasound energy beam isoriented with respect to a direction of flow in the blood vessel.
 17. Amethod of applying heat to a region proximate to a blood vessel, themethod comprising: generating an imaging ultrasonic beam adapted toimage a blood vessel target; receiving a reflection of the imagingultrasonic beam and in response producing a corresponding output signal;processing the output signal to identify a location of a treatment zoneproximate an outer wall of the blood vessel target; detecting thepresence of a nerve structure by applying an ultrasonic pulse to thetreatment zone, the ultrasonic pulse having an intensity that is lessthan 1,000 Watts per square centimeter; applying a therapeuticultrasound energy beam to the treatment zone, wherein the ultrasoundenergy beam is a high intensity focused ultrasound energy beam; andmoving the therapeutic ultrasound energy beam to over-scan the treatmentzone with therapeutic ultrasonic energy, wherein the imaging ultrasonicbeam, the ultrasonic pulse, and the therapeutic ultrasound energy beamare transcutaneously applied.
 18. The method of claim 17, wherein thepresence of the nerve structure is determined based on the pain of apatient in response to the ultrasonic pulse.
 19. The method of claim 17,wherein a direction of the therapeutic ultrasound energy beam isoriented with respect to a direction of flow in the blood vessel. 20.The method of claim 17, wherein the therapeutic ultrasound energy beamis movable in a plurality of directions at any given time.
 21. Themethod of claim 17, wherein the therapeutic ultrasound energy beam isapplied by an ultrasonic transducer applicator.
 22. The method of claim21, wherein the ultrasonic transducer applicator comprises an array oftransducers.
 23. The method of claim 22, wherein the array oftransducers is configured to emit the imaging ultrasonic beam.
 24. Themethod of claim 17, further comprising the step of interrupting theapplication of the therapeutic ultrasound beam to generate a secondimaging ultrasonic beam to confirm that the therapeutic ultrasound beamis being directed to the treatment zone.
 25. A method of treating apatient, the method comprising: directing an imaging ultrasonic beamproximate a blood vessel; receiving a reflection of the imagingultrasonic beam; processing the reflection of the imaging ultrasonicbeam to identify a location of a treatment zone proximate an outer wallof the blood vessel; detecting the presence of a nerve structure byapplying an ultrasonic pulse to the treatment zone, the ultrasonic pulsehaving an intensity that is less than 1,000 Watts per square centimeter;applying a high intensity focused ultrasound beam to the treatment zone;and moving the high intensity focused ultrasound beam to over-scan thetreatment zone with therapeutic ultrasonic energy, wherein the imagingultrasonic beam, the ultrasonic pulse, and the therapeutic ultrasoundenergy beam are transcutaneously applied.
 26. The method of claim 25,wherein the high intensity focused ultrasound beam is movable in aplurality of directions at any given time.
 27. The method of claim 25,wherein the high intensity focused ultrasound beam is applied by anultrasonic transducer applicator.
 28. The method of claim 27, whereinthe ultrasonic transducer applicator comprises an array of transducers.29. The method of claim 28, wherein the array of transducers isconfigured to emit the imaging ultrasonic beam.
 30. The method of claim25, further comprising the step of interrupting the application of thehigh intensity focused ultrasound beam to generate a second imagingultrasonic beam to confirm that the high intensity focused ultrasoundbeam is being directed to the treatment zone.